Cues for Cocaine and Normal Pleasures Activate Common Brain Sites

By Patrick Zickler, NIDA NOTES Staff Writer

Positron emission tomography shows that limbic regions in the brains of in-treatment cocaine users are activated by watching cocaine-related videos. Watching videos of nature scenes does not result in activation of these regions. This suggests that cue-induced craving for cocaine reflects activity in specific regions of the brain.(Greater activation is denoted by colors at the top end of the scale to right.)

Cocaine abusers may experience a powerful urge to take the drug when they encounter environmental cues such as people, places, or paraphernalia that they associate with drug use. This cue-induced craving may be accompanied by physical sensations-light-headedness, increased heart rate, or a mild drug-like "high"-like those produced by cocaine.

The similarity of cue-induced sensations to those of actual cocaine use suggests that some of the brain structures affected by cocaine are also affected by cocaine-related cues. Now, NIDA-supported research using two brain imaging techniques has shown that limbic regions of the brain, where cocaine is thought to produce its pleasurable effects by disrupting normal action of the brain chemical dopamine, also are activated by viewing videos containing cocaine-related scenes. Moreover, one study indicates that cues related to normal pleasures, such as sex, also activate the same sites.

Cocaine Cues Activate Sites in Limbic Region

At the University of Pennsylvania in Philadelphia, Dr. Anna Rose Childress and her colleagues used positron emission tomography (PET), which measures cerebral blood flow, to detect activation of nerve cells in the brain, to monitor the effect of cocaine-related cues on activity in limbic regions of the brain.

Participants in the study-14 adult male in-treatment cocaine users and 6 adult males who had never used cocaine-underwent PET imaging while watching a 25-minute video that contained images and sounds of simulated purchase, preparation, and smoking of crack cocaine. During the same imaging session, the participants watched a 25-minute nature travelog. Before and after watching each video, the men rated their feelings of drug-like high, craving for drugs, relaxation or tension, and general sense of well-being. The cocaine group, but not the non-cocaine group, reported craving and a drug-like high during the drug-related video. The nature video produced no subjective drug-like sensations in either group.

"The cocaine video that induced drug craving was associated with increased activation of two of the brain's limbic regions, the amygdala and the anterior cingulate, in the cocaine patients," Dr. Childress says.

"Cocaine craving does not merely act on the brain's reward circuits, but also takes over these sites and in essence rewrites normal emotionally driven preferences."

Cocaine abusers showed increased limbic activation when watching the video containing cocaine-related scenes, but not when watching the nature video. The participants who had never used cocaine showed no limbic activation when viewing either the cocaine-related or nature video.

"Activation of these two limbic regions during cue-induced craving is consistent with the role they play in mood, emotional response, and reward learning," Dr. Childress says. The regions also play a part in establishing associations between environmental signals and biologically significant stimuli such as food, sexual partners, and pain, Dr. Childress says, and are linked to the nucleus accumbens, a brain structure involved in associating behaviors and pleasurable rewards. "The interconnectedness of these regions makes it possible to experience the pleasures of rewards and to recognize opportunities to obtain them," she says. If common sites are involved in both normal and drug-related stimulus and response, this could pose problems for some potential pharmacological approaches to treating cocaine addiction, according to Dr. Childress. "Medications designed to block the limbic activation might reduce cocaine craving, but patients might be less likely to take the medication if it also blunts mood and motivation," she says.

Cues for Cocaine and Sex Act On Same Sites

At the Medical College of Wisconsin in Milwaukee, Dr. Elliot Stein and his colleagues used functional magnetic resonance imaging (fMRI), which measures blood oxygen levels, to show that the same limbic regions activated by cocaine and cocaine-related videos also are activated by videos containing scenes of normal nondrug stimulus. In this study, 31 adult males-17 cocaine users and 14 nonusers-watched 4-minute films depicting either drug use, nature scenes, or explicit sexual activity. Participants completed brief questionnaires describing their reactions to each film.

Functional magnetic resonance imaging shows activation of the same brain sites in cocaine addicts watching a cocaine-craving-inducing film (left) and non-drug-using subjects watching a film depicting explicit sexual scenes (right). This suggests that cue-induced cocaine craving and sexual excitement are associated with the same brain sites.

Cocaine users reported craving while viewing the film depicting drug use, and fMRI data revealed increased activation of sites in the limbic and other regions of their brains. These regions showed far less activation in nonusers viewing the same film. Both groups reported excitement while watching the sex film, although the levels of excitement were lower for drug users. Imaging revealed similar patterns of brain activation in both groups while watching the sex video, with less intense activation among drug users. There were no differences between users and nonusers when viewing the nature film.

"Most of the brain regions identified through fMRI as cocaine craving sites were similarly activated by the sexual stimulus. This suggests that common brain circuits are involved in response to drug and nondrug arousing stimuli," Dr. Stein says. "The fact that cocaine users' brains exhibited relatively weak activation in response to the sex film suggests that cocaine craving does not merely act on the brain's reward circuits, but also takes over these sites and in essence rewrites normal emotionally driven preferences," Dr. Stein says.

The fact that cocaine cues seem to act on brain sites associated with emotional response, information processing, and working memory may be relevant to development of treatment approaches. "On an optimistic note, it suggests that what we know about normal learning, memory, and emotions could be usefully applied to cue-induced craving and the development of appropriate pharmacological, behavioral, and cognitive therapies," Dr. Stein says.